Evidence map›Paper›PMID 41200820›Full record

ArticleCirculation. Genomic and precision medicine2025

Plasma Protein Profile Associated With a Family History of Early-Onset Coronary Heart Disease.

Agnes Wahrenberg, Lars Lind, Natan Åberg, Henrike Häbel, Marika Ström, Anders Mälarstig, Patrik K E Magnusson, Ralf Kuja-Halkola, Göran Bergström, Gunnar Engström and 5 more

Abstract read
In one paragraph

Article in Circulation. Genomic and precision medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Agnes WahrenbergDepartment of Clinical Science and Education, Södersjukhuset (A.W., N.Å., P.S.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-1183-9798
Lars LindDepartment of Medical Sciences, Clinical Epidemiology (L.L.), Uppsala University, Sweden.ORCID 0000-0003-2335-8542
Natan ÅbergDepartment of Clinical Science and Education, Södersjukhuset (A.W., N.Å., P.S.), Karolinska Institutet, Stockholm, Sweden.
Henrike HäbelDepartment of Learning, Informatics, Management and Ethics (H.H., M.S.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-5564-4258
Marika StrömDepartment of Learning, Informatics, Management and Ethics (H.H., M.S.), Karolinska Institutet, Stockholm, Sweden.ORCID 0009-0002-1512-7891
Anders MälarstigDepartment of Medical Epidemiology and Biostatistics (A.M., P.K.E.M., R.K.-H.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-2608-1358
Patrik K E MagnussonDepartment of Medical Epidemiology and Biostatistics (A.M., P.K.E.M., R.K.-H.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-7315-7899
Ralf Kuja-HalkolaDepartment of Medical Epidemiology and Biostatistics (A.M., P.K.E.M., R.K.-H.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-3765-2067
Göran BergströmDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden (G.B.).ORCID 0000-0003-4289-5722
Gunnar EngströmDepartment of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Sweden (G.E.).ORCID 0000-0002-8618-9152
Emil HagströmDepartment of Medical Sciences, Cardiology (E.H.), Uppsala University, Sweden.ORCID 0000-0003-3221-0144
Tomas JernbergDepartment of Clinical Sciences, Danderyd University Hospital (T.J.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-1695-379X
Stefan SöderbergDepartment of Public Health and Clinical Medicine, Cardiology, Umeå University, Sweden (S.S.).ORCID 0000-0001-9225-1306
Carl Johan ÖstgrenCenter of Medical Image Science and Visualization (C.J.O.), Linköping University, Sweden.ORCID 0000-0003-1617-3179
Per SvenssonDepartment of Clinical Science and Education, Södersjukhuset (A.W., N.Å., P.S.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-0372-6272

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProteins linked to heritable coronary heart disease (CHD) could uncover new pathophysiological mechanisms of atherosclerosis. We report on the protein profile associated with a family history of early-onset CHD and whether the relation between proteins and coronary atherosclerotic burden differs according to family history status, as well as inferences from Mendelian randomization.

methodsData on coronary atherosclerotic burden from computed tomography angiography and Olink proteomics were retrieved for 4521 subjects, free of known CHD, from SCAPIS (the Swedish Cardiopulmonary Bioimage Study). Records of myocardial infarction and coronary revascularization therapies in any parent or sibling of subjects were retrieved from national registers. Linear associations between family history and proteins were adjusted for age, sex, and study site. Statistical interactions between proteins and family history for the association between proteins and the coronary atherosclerotic burden were also studied. Mendelian randomization for causal associations between proteins and CHD was performed with genome-wide association study summary data from UKB-PPP (UK Biobank Pharma Proteomics Project), CARDIoGRAMplusC4D, and FinnGen.

resultsOf 4251 subjects, family history of early-onset CHD was present in 9.5%. Thirty-eight proteins, with biological features of inflammation, lipid metabolism, and vascular function, were associated with family history using a false discovery rate of 0.05. The strongest associations were observed with cathepsin D, paraoxonase 3, renin andfollistatin, neither of which was attenuated by adjusting for cardiovascular risk factors. Eighteen proteins were statistical interactors with family history in the association between each protein and the coronary atherosclerotic burden, most notably the LDL (low-density lipoprotein) receptor, transferrin receptor protein 1, and PECAM1 (platelet endothelial cell adhesion molecule 1). In 2-sample Mendelian randomization, a novel association was found for follistatin and myocardial infarction, and previous associations for PCSK9 (proprotein convertase subtilisin/kexin type 9) and PECAM1 were repeated.

conclusionsThese findings highlight new potential mechanisms for heritable and general atherosclerosis.

Indexed as

Blood ProteinsCoronary Artery DiseaseCoronary DiseaseAdultAge of OnsetFemaleGenome-Wide Association StudyHumansMaleMendelian Randomization AnalysisMiddle AgedBlood Proteinscardiovascular diseasescoronary artery diseasefollistatinMendelian randomization analysismyocardial infarction

Identifiers

PMID41200820
PMCPMC12711270

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.